Past pandemics may offer clue to A/H1N1 response

May - June, 2009 | Volume 8, Issue 3

Using data from three 20th century flu pandemics, Fogarty researchers working closely with Mexican counterparts are suggesting that policy makers target young-to-middle-age adults if there is not enough vaccine to fight the novel A/H1N1 virus in coming months.

In articles appearing in the New England Journal of Medicine and Science, members of Fogarty's division of international epidemiology and population studies examined the new outbreak of influenza reported in Mexico this spring and compared it to the pandemics of 1889-1892,1918-1919, 1957-1963 and 1968-1970.

Dr. Mark Miller, the division's director and lead author, said the 20th century pandemics shared certain features: a shift in virus subtype, successive waves of illness, higher transmission rates than seasonal flu and different geographic impacts. But their most striking characteristic was the shift in mortality toward younger ages.

Different age risks

While older people are more at risk from seasonal flu, "The role of pre-existing antibodies in the elderly, their reduced immune response because of immune senescence and greater influenza transmission among children should prompt the targeting of younger age groups as the soundest policy in a 1918-like scenario," said Miller and coauthors Dr. Cecile Viboud and Dr. Marta Balinska of Fogarty and Dr. Lone Simonsen of The George Washington University.

At a meeting of Fogarty scientists, Miller suggested that exposure to viruses circulating before the 1957 pandemic by people now over 50 years old might account for their relative protection compared to younger populations.

Because of long-standing ties with Mexican health authorities, Miller's group became involved immediately in the effort to track the spring outbreak. "We had already been working with Mexican colleagues for many years and had the privilege of helping them with the analysis of this outbreak."

While not predicting the future severity of A/H1N1, the article did emphasize that advance knowledge of increased risk by age can prepare officials to respond more effectively.

A team led by researchers from the CDC, which included Fogarty research fellows Dr. Colin Russell and Dr. Derek J. Smith, reported in Science that the new flu contains genes that have been circulating in swine since 1998.

"The evolutionary distances between the gene segments of this virus and its closest relatives indicate a lack of surveillance in swine populations that may harbor influenza viruses with pandemic potential," they said.

Unlike 1976 flu

An A/H1N1 strain, popularly called "swine flu," caused a pandemic scare in the United States in 1976. But Miller says unlike that outbreak, the 2009 virus is novel because it shows evidence of sustained transmission among humans.

"The death toll of a future pandemic depends not only on the virulence of the virus in question but also on the rapidity with which we are able to introduce effective preventive and therapeutic measures," Miller and colleagues said in the June 18 New England Journal article.

They called for active real-time surveillance around the world and for international cooperation in developing and best using limited vaccine supplies during periods between waves of any outbreak.

"If an effective vaccine had been available even a year after emergence of the 1968 A/H3N2 virus, most of the deaths in Europe and Asia could probably have been prevented," he and his colleagues said.

Nonmedical interventions such as "social distancing" could be effective, according to mathematical simulations, they said, but only if the virus has a lower reproduction rate than occurred in the previous pandemics.

Workshop in Africa

Miller, Viboud, along with Fogarty research fellows Dr. Katharine Sturm-Ramirez, Dr. Martha Nelson, Dr. Eddie Holmes and Dr. Colin Russell and Dr. Maria Giovanni from the National Institute of Allergy and Infectious Diseases (NIAID) led a workshop in Senegal to introduce African researchers to new methods of analyzing influenza patterns the same week that news of the A/H1N1 outbreak swept the world.

It was the first meeting in Africa of the Multinational Influenza Seasonal Mortality Study Initiative (MISMS) that Fogarty leads. Researchers from 13 countries attended the sessions, cosponsored by the Institut Pasteur de Dakar with participation from its Paris-based scientists as well.

Miller, Mark A., Viboud, Cecile, Balinska, Marta, Simonsen, Lone. "The Signature Features of Influenza Pandemics—Implications for Policy." New England Journal of Medicine, Volume 360:2595-2598, June 18, 2009.

Rebecca J. Garten et al. "Antigenic and Genetic Characteristics of Swine-Origin 2009 A(H1N1) Influenza Viruses Circulating in Humans." Science, May 2009, published online May 22, 2009.

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